This research project was designed to gain insight into the mechanism(s) of proteinuria in NZB/W hybrid mice, an animal model of spontaneous immune complex glomerulonephritis. Increase in glomerular permeability will be assessed by means of probe molecules of known molecular size (horseradish peroxidase, catalase and ferritin) injected systemically and detected in tissues and by urinary protein quantitation and characterization. The specific objectives are: 1) to define the route and extent of protein leakage during the induction and progression of glomerulonephritis; 2) to determine whether slit diaphragm substructure alterations and decrease in sialic acid content of pedicels occur prior to and/or during glomerular permeability increase and 3) to correlate glomerular permeability characteristics with such features as: altered glomerular structure and histochemical (sialic acid) composition, immunopathologic, serologic and clinical findings. The rationale is based upon a body of experimental evidence indicating that during the proteinuric state the glomerulus is more permeable to a variety of substances. It is anticipated that changes in slit pore complex, mediated by a variety of agents, including immunologic mechanisms, might be, at least in part, responsible for protein leakage. In addition, it is expected that the glomerular basement membrane be more permeable to such tracers, probably at the vicinity or in areas immune complexes are deposited.